ANN ARBOR, MI — Oral pre-exposure prophylaxis (PrEP) for human immunodeficiency virus (HIV) gained Food and Drug Administration approval in 2012, and many commentators hailed the therapy as a “once-in-a-generation” advance. Despite its promise, cost concerns and other controversies have limited its adoption, but a recent VA study might help clinicians target patients most likely to benefit from the therapy.

The PrEP combination of emtricitabine and tenofovir has been used for more than 10 years as part of the antiretroviral therapy for individuals who already have HIV. It blocks reverse transcriptase, which the virus uses to reproduce.

PrEP also prevents HIV-negative individuals from acquiring the virus. Studies that evaluated the therapy among high-risk men who had sex with men found a significant variance in effectiveness. An early study, iPrEx, showed the combination was 44% effective in preventing HIV infection, although analysis indicated that all of the study participants who contracted HIV had not taken the drug as prescribed and that proper use can reduce the risk of infection by 92%. Two major studies in 2015, PROUD and IPERGAY, put the drug’s effectiveness at 86%.1, 2, 3

“Among heterosexuals, the effectiveness appears to be about 69%. But, with the range in the studies to date, I don’t feel like I can give my patients an actual number, so I give a range of effectiveness,” said Sandro K. Cinti, MD, of the VA Ann Arbor Health System and professor of infectious diseases at the University of Michigan Health System. “It may take a while to get data from its use in clinical settings where we’re not controlling everything.”

Physicians who treat high-risk individuals might not recommend the drug to everyone for whom it is indicated, in part because of its substantial cost. The retail price of the combination drug ranges from $1,300 to $1,500 per month, though most insurance companies cover a significant percentage of the cost, and the manufacturer offers discounts to the uninsured. The VA, which provides care to more than 40,000 veterans with HIV, pays a substantially lower rate, based on the large volume of patients already taking the combination as part of their antiretroviral therapy combination.

To help physicians determine which patients should take PrEP, Cinti and his colleagues, Eric Ross and David Hutton, PhD, of the University of Michigan Medical School, calculated the cost-effectiveness of the therapy in a study published in the March issue of the Journal of AIDS.4

The researchers used a mathematical model employing the Centers for Disease Control and Prevention’s HIV Incidence Risk Index for men who have sex with men (HIRI-MSM) questionnaire to assess cost-effectiveness. The simulations looked at strategies that used no PrEP, PrEP available to all MSM and eligibility thresholds based on HIRI-MSM scores from 5 to 45, in increments of 5.

The study evaluated PrEP efficacies from 44% to 86% and annual costs from $5,900 to $8,700, based on the effectiveness rates and costs of the IPrEx, IPERGAY and PROUD studies. Strategies were considered cost-effective, if the incremental cost-effectiveness ratio (ICER) was greater than or equal to $100,000/quality-adjusted life-year (QALY).

If all MSM were offered PrEP, the analysis found that the therapy would prevent 33.5% of new cases of HIV over a 20-year period at a cost of $1,474,000 per QALY. Across all cost and effectiveness assumptions, offering PrEP to individuals with HIRI-MSM scores at or above 25 proved optimal. Low cost/high efficacy assumptions dropped the cost-effective threshold to 15 or 20.

While the analysis can provide some additional guidance to clinicians, it likely will not resolve the debate about who should take PrEP, even among the researchers involved in the study.

“We come out in the article saying that a cost-effective score for MSM seems to be 25. The CDC recommends PrEP for individuals with a score of 10 or more,” said Cinti. “If I were counseling someone, I would not say they don’t have enough of a risk factor if they’re under 25. While the risks are pretty low, I would still give PrEP to a patient at 10.”

The study might help policymakers and others talk more meaningfully about the broader economic issues involved in prophylactic treatment of HIV, said Cinti, including cost-effectiveness in big populations and relative value to other methods of reducing transmission.

“We are hoping we will see a decrease in new infections in the U.S., which have held steady at about 50,000 new cases a year,” said Cinti. “PrEP may be a way to do that, but it’s still too early to know. We’ll have a better idea once primary care doctors take over PrEP, as that will make it more accessible” to high risk individuals who may not be coming to specialty clinics.

Much of the controversy about PrEP revolves around its potential to reduce the use of condoms among MSM, a concern that has led the AIDS Healthcare Foundation to criticize the therapy’s potential to increase the risk of other sexually-transmitted infections, such as syphilis and gonorrhea.

“Even for MSM on PrEP, I wouldn’t say that it’s safe to have unprotected sex,” Cinti said. “Condoms used appropriately at all times are 90% to 95% protective, which is much better than even the two best studies on PrEP. If condoms are used exactly as recommended, PrEP doesn’t add much protection, but most men at high risk are not having protected sex all the time; therefore, PrEP is helpful.”

Cinti also noted that patients who do become infected with HIV while on PrEP could develop resistance to the medication. Because PrEP also increases the risk of renal dysfunction, he recommends monitoring users very closely, with screenings for other sexually-transmitted diseases every three months, as well as ongoing discussions of condom use and sexual practices and liver and kidney testing every six months. “Patients are often surprised by how much follow-up is needed,” he said.

In addition, Cinti urges clinicians to perform frequent testing for HIV among MSM and other high-risk groups. “A lot of transmission is among those who are undiagnosed, which we estimate to be about 25% of those infected,” he pointed out. “If we can identify infected individuals and get their viral loads down to undetectable levels, then transmission rates drop more than 90%.”